This project will focus on the preparation and evaluation of nonthrombogenic, antibacterial nitric oxide (NO) releasing catheters. Phase 1 of this SBIR will: 1) develop unique NO secreting catheters (14-20 gauge); 2) test them in rabbit and sheep models to evaluate thrombogenicity and bacterial adherence; Phase 2 will scale up manufacturing and evaluate toxicity in preparation for human trials. The rationale for this research is to mimic the function of the endothelium. Low levels of NO released by the normal endothelium inhibit platelet adhesion and activation, thus preventing thrombus formation. Further, it has been shown that NO at low doses exhibits significant bactericidal activity. Hence, the preparation of catheters that secrete NO will solve two longstanding problems in the care of critically ill patients. The basic NO release polymer technology that employs novel diazeniumdiolate type NO donors has been developed in laboratories at the University of Michigan (U of M) over the past 10 years. Successful applications of this technology have already included the development of anti-platelet coatings for extracorporeal circulation devices and the preparation more biocompatible implantable chemical sensors with improved analytical performance. Via collaboration with the research team at the U of M that has been working on this technology, MC3 now intends to develop and test catheters that release NO at controlled rates in order to prevent thrombosis and infection, two major problems associated with the use of catheters. PUBLIC HEALTH RELEVANCE: Clotting and infection is a major problem in intravascular (IV) catheters. Normal blood vessels secrete a chemical called nitric oxide which prevents these problems. This research will develop 14-20 gauge catheters which secrete nitric oxide, decreasing the risk of clotting and infection.